1. Using magnetic resonance imaging (MRI), we demonstrated atrophy of the corpus callosum, a marker of neocortical neuronal loss, in nondemented Down syndrome (trisomy 21) adults compared with age-matched healthy controls. Down syndrome subjects are at risk for Alzheimer disease, due to duplication of the amyloid precursor protein (APP) gene on chromosome 21. Measuring corpus callosum volume with MRI could help to identify subjects in the general population with mild cognitive insufficiency who later will develop Alzheimer disease. 2. Automated voxel-based morphometry was used to analyze structural magnetic resonance images of brains from 27 non-demented Down syndrome adults, an at-risk group for Alzheimer disease, of different ages. In this group, grey matter volume declined with advancing age in numerous cortical regions, suggesting that brain atrophy occurs and progresses before clinical dementia becomes evident in Down syndrome.